The interactions of macrophages and T lymphocyte subpopulations in the generation of an immune response will be studied. Use will be made of a model system in which the afferent, central, and efferent phases of the immune response to protein antigens or haptens are analyzed separately. Initiator T lymphocytes (TI) are induced in vitro by antigen-pulsed or hapten-modified macrophages. The cellular nature of the TI cells will be studied using antisera and monoclonal antibodies against discrete T cell subsets, as well as selective drugs. The TI cells recruit in vivo a second population of antigen-reactive T lymphocytes. The recruited cell population(s) will be similarly characterized and its functional activity delineated. The ability of recruited T cells to act as helper cells for B cells in antibody production, helper cells for T cells in the generation of cytotoxic cells, or as cells mediating delayed hypersensitivity will be tested. In addition, the effects of antigen priming and tolerance on the behavior of initiator and recruited T lymphocytes will be determined.